The Effect of Intravenous Lidocaine on QTc Changes During Spinal Anesthesia in Elderly Patients

Prolonged QT interval may lead to serious arrhythmias and ventricular fibrillation, hence prevention of the QT-interval prolongation is crucial for physicians. The aim of this study was to assess the influence of intravenous lidocaine on the QTc interval resulting from spinal anesthesia with bupivacaine. In a randomized double blind trial, fifty male patients with mean age of 70.38 and ASA physical status ΙΙ, who underwent spinal anesthesia for elective orthopedic lower limb surgical procedures, were assessed. Our subjects were divided into two groups, patients randomly received intravenously either 1.5 mg/kg lidocaine 2% as test group (n=25), or 0.05 ml/kg isotonic sodium chloride as control group (n=25), just before inducing of spinal anesthesia. Spinal anesthesia was performed in the sitting position with 3 ml of 0.5% hyperbaric bupivacaine. Values of the QTc interval, heart rate, and arterial blood pressure were measured before spinal anesthesia as well as 1, 5, 15, and 30 minutes after spinal anesthesia. With respect to the within-group values, statistically significant prolongation of the QTc interval as well as hemodynamic variability were detected in the measured times after blockade. There was no statistical difference between two groups according to hemodynamic parameters and the duration of the QTc interval before spinal anesthesia and times after spinal block with bupivacaine. Administration of intravenous lidocaine may not prevent the prolongation of the QTc interval and hemodynamic changes resulting from spinal anesthesia with hyperbaric bupivacaine, in elderly subject

Termination of pregnancy in a twin pregnant patient with COVID-19

In this article, we present a pregnant case suspected of COVID-19 with underlying symptoms of respiratory distress; which was referred to Shohada-e-Tajrish Hospital. Due to the progressive decrease of O2 saturation, the medical team decided to terminate the pregnancy to save the patient's life. Despite all these efforts including pharmaceutical agents, the patient passed away

The liver-derived exosomes stimulate insulin gene expression in pancreatic beta cells under condition of insulin resistance

Introduction: An insufficient functional beta cell mass is a core pathological hallmark of type 2 diabetes (T2D). Despite the availability of several effective pharmaceuticals for diabetes management, there is an urgent need for novel medications to protect pancreatic beta cells under diabetic conditions. Integrative organ cross-communication controls the energy balance and glucose homeostasis. The liver and pancreatic islets have dynamic cross-communications where the liver can trigger a compensatory beta cell mass expansion and enhanced hormonal secretion in insulin-resistant conditions. However, the indispensable element(s) that foster beta cell proliferation and insulin secretion have yet to be completely identified. Exosomes are important extracellular vehicles (EVs) released by most cell types that transfer biological signal(s), including metabolic messengers such as miRNA and peptides, between cells and organs. Methods: We investigated whether beta cells can take up liver-derived exosomes and examined their impact on beta cell functional genes and insulin expression. Exosomes isolated from human liver HepG2 cells were characterized using various methods, including Transmission Electron Microscopy (TEM), dynamic light scattering (DLS), and Western blot analysis of exosomal markers. Exosome labeling and cell uptake were assessed using CM-Dil dye. The effect of liver cell-derived exosomes on Min6 beta cells was determined through gene expression analyses of beta cell markers and insulin using qPCR, as well as Akt signaling using Western blotting. Results: Treatment of Min6 beta cells with exosomes isolated from human liver HepG2 cells treated with insulin receptor antagonist S961 significantly increased the expression of beta cell markers Pdx1, NeuroD1, and Ins1 compared to the exosomes isolated from untreated cells. In line with this, the activity of AKT kinase, an integral component of the insulin receptor pathway, is elevated in pancreatic beta cells, as represented by an increase in AKT’s downstream substrate, FoxO1 phosphorylation. Discussions: This study suggests that liver-derived exosomes may carry a specific molecular cargo that can affect insulin expression in pancreatic beta cells, ultimately affecting glucose homeostasis

The Significance of Matrix Metalloproteinases in the Immunopathogenesis and Treatment of Multiple Sclerosis

Multiple sclerosis (MS) is an autoimmune disease of the central nervous system (CNS). The major pathological outcomes of the disease are the loss of blood-brain barrier (BBB) integrity and the development of reactive astrogliosis and MS plaque. For the disease to occur, the non-resident cells must enter into the immune-privileged CNS through a breach in the relatively impermeable BBB. It has been demonstrated that matrix metalloproteinases (MMPs) play an important role in the immunopathogenesis of MS, in part through the disruption of the BBB and the recruitment of inflammatory cells into the CNS. Moreover, MMPs can also enhance the cleavage of myelin basic protein (MBP) and the demyelination process. Regarding the growing data on the roles of MMPs and their tissue inhibitors (TIMPs) in the pathogenesis of MS, this review discusses the role of different types of MMPs, including MMP-2, -3, -7, -9, -12 and -25, in the immunopathogenesis and treatment of MS

The Role of Inflammatory Mediators in the Pathogenesis of Alzheimer’s Disease

Alzheimer’s disease (AD), a neurodegenerative disorder associated with advanced age, is the most common cause of dementia globally. AD is characterised by cognitive dysfunction, deposition of amyloid plaques, neurofibrillary tangles and neuro-inflammation. Inflammation of the brain is a key pathological hallmark of AD. Thus, clinical and immunopathological evidence of AD could be potentially supported by inflammatory mediators, including cytokines, chemokines, the complement system, acute phase proteins and oxidative mediators. In particular, oxidative mediators may actively contribute to the progression of AD and on-going inflammation in the brain. This review provides an overview of the functions and activities of inflammatory mediators in AD. An improved understanding of inflammatory processes and their role in AD is needed to improve therapeutic research aims in the field of AD and similar diseases

Primary ciliary dyskinesia in six patients with bronchiectasis

INTRODUCTION: Primary ciliary dyskinesia [PCD] is generally considered as a rare autosomal recessive disorder. Previous studies reported various prevalence of PCD among patients with bronchiectasis. MATERIAL AND METHODS: Six PCD patients who were diagnosed during the investigation of 40 patients with bronchiectasis were enrolled in this study. Ultra structural studies for both epithelium and cilia were performed, and the deformities in detailed electron microscopic images confirmed the diagnosis of PCD. RESULTS: Four patients experienced the first symptoms shortly after the birth, 1 by the age of 1 and 1 by the age of 4 years. Except of 1 case that was diagnosed 2 months after the onset of disease, diagnosis delay was longer than 5 years in all patients. Consanguineous marriage was observed in the parents of all patients. Upper respiratory tract infections were documented for all patients. CONCLUSIONS: PCD should be considered as a probable underlying disorder in patients with bronchiectasis. Past medical history of otitis media and history of similar clinical findings in family members should raise suspicion toward PCD.INTRODUCTION: Primary ciliary dyskinesia [PCD] is generally considered as a rare autosomal recessive disorder. Previous studies reported various prevalence of PCD among patients with bronchiectasis. MATERIAL AND METHODS: Six PCD patients who were diagnosed during the investigation of 40 patients with bronchiectasis were enrolled in this study. Ultra structural studies for both epithelium and cilia were performed, and the deformities in detailed electron microscopic images confirmed the diagnosis of PCD. RESULTS: Four patients experienced the first symptoms shortly after the birth, 1 by the age of 1 and 1 by the age of 4 years. Except of 1 case that was diagnosed 2 months after the onset of disease, diagnosis delay was longer than 5 years in all patients. Consanguineous marriage was observed in the parents of all patients. Upper respiratory tract infections were documented for all patients. CONCLUSIONS: PCD should be considered as a probable underlying disorder in patients with bronchiectasis. Past medical history of otitis media and history of similar clinical findings in family members should raise suspicion toward PCD

Evaluation and comparison of immunization level between recombinant proteins of binding subunit of entrotoxigenic Escherichia coli and botulinum toxin

زمینه و هدف: در میان عوامل باکتریایی، شایع ترین عامل بیماری اسهال، باکتری اشریشیاکلی انتروتوکسیژنیک است. زیر واحد LTB سم این باکتری قادر به ایجاد مصونیتی شش ماهه است. کلستریدیوم بوتولینوم نیز عامل بیماری کشنده بوتولیسم می باشد و زیر واحد BoNT/A-Hc سم آن می تواند تا دو سال در برابر این بیماری مصونیت ایجاد کند. میزان ایمنی زایی که هر یک از این زیر واحدهای نوترکیب ایجاد می کنند، می تواند از عواملی باشد که در به وجود آمدن مصونیتی با ماندگاری متفاوت تأثیرگذار باشد. هدف از این مطالعه بررسی و مقایسه میزان تولید آنتی بادی ناشی از استفاده از دو پروتئین LTB و BONT/A-Hc در موش آزمایشگاهی بود. روش بررسی: در این مطالعه تجربی از باکتری Bl21DE3 E. Coli تراریخت شده با وکتور pET28aاستفاده گردید. این وکتور حاوی ژن نوترکیب LTB اشریشیاکلی انتروتوکسیژنیک و ژن نوترکیب BONT/A-Hc بوتولینوم به طور جداگانه بود. پس از بهینه سازی بیان و تخلیص پروتئین نوترکیب LTB از فاز نامحلول و BoNT/A-Hc از فاز محلول عصاره سلولی، محصولات آن ها بر روی ژلSDS-PAGE بررسی گردید. موش های آزمایشگاهی به وسیله پروتئین های حاصل، ایمنی زایی شدند. تیتر آنتی بادی حاصل از هر دو نوع پروتئین نوترکیب با استفاده از آزمون آماری t-Test در نرم افزار SPSS ارزیابی و مورد مقایسه قرار گرفت. یافته ها: پروتئین های نوترکیب بیان شده BoNT/A-Hc و LTB با ستون نیکل تخلیص شدند. پس از ایمنی زایی موش های آزمایشگاهی، تفاوت معناداری در تیتر آنتی بادی برای دو پروتئین BoNT/A-Hc و LTB مشاهده گردید (01/0>P). نتیجه گیری: اختلاف کمی بین تیتر آنتی بادی برای دو پروتئین BoNT/A-Hc و LTB مشاهده گردید که می تواند به دلیل خاصیت قوی ادجوانسیتی LTBو ایمنی زایی ایجاد شده تقریباً یکسان، در فاصله زمانی محدود باش

Therapeutic effects of D-aspartate in a mouse model of multiple sclerosis

Abstract Experimental autoimmune encephalomyelitis (EAE) is an animal model of multiple sclerosis. EAE is mainly mediated by adaptive and innate immune responses that leads to an inflammatory demyelization and axonal damage. The aim of the present research was to examine the therapeutic efficacy of D-aspartic acid (D-Asp) on a mouse EAE model. EAE induction was performed in female C57BL/6 mice by myelin 40 oligodendrocyte glycoprotein (35-55) in a complete Freund's adjuvant emulsion, and D-Asp was used to test its efficiency in the reduction of EAE. During the course of study, clinical evaluation was assessed, and on Day 21, post-immunization blood samples were taken from the heart of mice for the evaluation of interleukin 6 and other chemical molecules. The mice were sacrificed, and their brain and cerebellum were removed for histological analysis. Our findings indicated that D-Asp had beneficial effects on EAE by attenuation in the severity and delay in the onset of the disease. Histological analysis showed that treatment with D-Asp can reduce inflammation. Moreover, in D-Asp-treated mice, the serum level of interleukin 6 was significantly lower than that in control animals, whereas the total antioxidant capacity was significantly higher. The data indicates that D-Asp possess neuroprotective property to prevent the onset of the multiple sclerosis

Developing Inference Model to Diagnosis of Primary Immunodeficiency Diseases in Protégé

Primary immunodeficiency diseases (PIDs) are a genetically  heterogeneous group disorders that affect distinct components of both humoral and cellular arms of the immune system (1,2). Overlapping signs and symptoms of these diseases is a challenge for diagnosis and treatment (3,4). Awareness of the  symptoms and considering   the   possibility   of   PID   in   differential diagnosis help to rapid recognition and more appropriate treatment   (2,5).   Timely   recognition   and   treatment reduced mortality and increased lifespan and quality of life of the patients (6). Memorization of all effective criteria to diagnosis is difficult, so developing a computerized program based on diagnosis criteria, improves significantly the quality of care (7,8).To develop the inference model to the diagnosis of PIDs, ontology has been used in this study. The study focused on eight common diseases of PIDs include Common Variable Immune Deficiency (CVID), X- Linked Agammaglobulinemia (Bruton’s) (XLA), Selective IgA Deficiency (SIgA), CD40L deficiency, UNG deficiency, Isolated immunoglobulin (Ig) G Subclass deficiency, Specific antibody deficiency (SAD) with normal Ig concentrations and normal numbers of B cells, Transient Hypogammaglobulinemia of infancy (THI) with normal numbers of B cells. Based on clinical guidelines  and   medical   literature   in   PID   (9),   we designed a checklist to extract and classified most important signs and symptoms, family history, and laboratory data for eight main type of primary antibody deficiencies   (PADs).   To   evaluate   the   quality   of checklist, data for 100 cases in a different type of PADs were tested. Using frame-based ontology modeling to create the inference model and "Noy and McGuinness" method to develop the inference model. "Noy and McGuinness" method includes seven stages (10). Below we describe each stage of the method

Does Serum Chloride Level Affect the Outcomes in Children Admitted to the Pediatric Intensive Care Unit?

Background: Serum chloride disorders are common in critically ill patients and appear to be associated with worse outcomes in patients. However, less attention has been paid to the amount of chloride in critically ill patients.  This study aims to determine the frequency of serum chloride disorders and their possible association with disease outcomes in all children admitted to the pediatric intensive care unit (PICU). Methods: This prospective study was performed on all patients admitted to the PICU of Akbar Children Hospital, Mashhad, Iran, from April 2019 to April 2020. Serum chloride levels were recorded daily on the first, second, and third days of the PICU stay. Statistical analyses were carried out using SPSS software (Version 24, SPSS Inc., Chicago, IL, USA) through one-way analysis of variance test, and Chi-square test in the significance level of α=0.05. Results: In this study, no significant relationship was observed between serum chloride levels and patients’ final status (P≥0.05). Serum Chloride level on the first day of PICU admission was significantly correlated with the length of PICU stay (r= 0.258, P= 0.029). There was no significant relationship between serum chloride levels and the patients’ need for mechanical ventilation on any of the three days (P≥0.05). Conclusions: According to the results, serum chloride level can be considered as an indicator of the length of the PICU stay